Aminolevulinic Acid-Based Tumor Detection and Therapy: Molecular Mechanisms and Strategies for Enhancement.


:Aminolevulinic acid (ALA) is the first metabolite in the heme biosynthesis pathway in humans. In addition to the end product heme, this pathway also produces other porphyrin metabolites. Protoporphyrin (PpIX) is one heme precursor porphyrin with good fluorescence and photosensitizing activity. Because tumors and other proliferating cells tend to exhibit a higher level of PpIX than normal cells after ALA incubation, ALA has been used as a prodrug to enable PpIX fluorescence detection and photodynamic therapy (PDT) of lesion tissues. Extensive studies have been carried out in the past twenty years to explore why some tumors exhibit elevated ALA-mediated PpIX and how to enhance PpIX levels to achieve better tumor detection and treatment. Here we would like to summarize previous research in order to stimulate future studies on these important topics. In this review, we focus on summarizing tumor-associated alterations in heme biosynthesis enzymes, mitochondrial functions and porphyrin transporters that contribute to ALA-PpIX increase in tumors. Mechanism-based therapeutic strategies for enhancing ALA-based modalities including iron chelators, differentiation agents and PpIX transporter inhibitors are also discussed.


Int J Mol Sci


Yang X,Palasuberniam P,Kraus D,Chen B




Has Abstract


2015-10-28 00:00:00












  • Identification of the high molecular weight isoform of phostensin.

    abstract::Phostensin is encoded by KIAA1949. 5'-RACEanalysis has been used to identify the translation start site of phostensin mRNA, indicating that it encodes 165 amino acids with an apparent molecular weight of 26 kDa on SDS-PAGE. This low-molecular-weight phostensin is present in human peripheral blood mononuclear cells and...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Lin YS,Huang HL,Liu WT,Lin TH,Huang HB

    更新日期:2014-01-15 00:00:00

  • Photobiomodulation of the Visual System and Human Health.

    abstract::Humans express an expansive and detailed response to wavelength differences within the electromagnetic (EM) spectrum. This is most clearly manifest, and most studied, with respect to a relatively small range of electromagnetic radiation that includes the visible wavelengths with abutting ultraviolet and infrared, and ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Buch J,Hammond B

    更新日期:2020-10-28 00:00:00

  • The Impact of O-Glycosylation on Cyanidin Interaction with RBCs and HMEC-1 Cells-Structure⁻Activity Relationships.

    abstract::With the aim of contributing to the knowledge about their potential therapeutic activity, we determined the biological activities of cyanidin and its selected O-glycosides in relation to erythrocytes (RBCs) and human dermal vascular endothelial cells (HMEC-1). Furthermore, on the basis of changes in the physical/funct...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Cyboran-Mikołajczyk S,Solarska-Ściuk K,Mieszała K,Glatzel-Plucińska N,Matczak K,Kleszczyńska H

    更新日期:2019-04-19 00:00:00

  • Crosstalk of the Brassinosteroid Signalosome with Phytohormonal and Stress Signaling Components Maintains a Balance between the Processes of Growth and Stress Tolerance.

    abstract::Brassinosteroids (BRs) are a class of phytohormones, which regulate various processes during plant life cycle. Intensive studies conducted with genetic, physiological and molecular approaches allowed identification of various components participating in the BR signaling-from the ligand perception, through cytoplasmic ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Gruszka D

    更新日期:2018-09-09 00:00:00

  • Nobiletin Inhibits Angiogenesis by Regulating Src/FAK/STAT3-Mediated Signaling through PXN in ER⁺ Breast Cancer Cells.

    abstract::Tumor angiogenesis is one of the major hallmarks of tumor progression. Nobiletin is a natural flavonoid isolated from citrus peel that has anti-angiogenic activity. Steroid receptor coactivator (Src) is an intracellular tyrosine kinase so that focal adhesion kinase (FAK) binds to Src to play a role in tumor angiogenes...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Sp N,Kang DY,Joung YH,Park JH,Kim WS,Lee HK,Song KD,Park YM,Yang YM

    更新日期:2017-04-30 00:00:00

  • In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation.

    abstract::Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable targe...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Thappeta KRV,Zhao LN,Nge CE,Crasta S,Leong CY,Ng V,Kanagasundaram Y,Fan H,Ng SB

    更新日期:2020-11-14 00:00:00

  • Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example.

    abstract::The wide employment of iron nanoparticles in environmental and occupational settings underlines their potential to enter the brain. Human cell-based systems are recommended as relevant models to reduce uncertainty and to improve prediction of human toxicity. This study aimed at demonstrating the in vitro differentiati...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: De Simone U,Spinillo A,Caloni F,Gribaldo L,Coccini T

    更新日期:2019-12-31 00:00:00

  • Investigating REPAIRv2 as a Tool to Edit CFTR mRNA with Premature Stop Codons.

    abstract::Cystic fibrosis (CF) is caused by mutations in the gene encoding the transmembrane conductance regulator (CFTR) protein. Some CF patients are compound heterozygous or homozygous for nonsense mutations in the CFTR gene. This implies the presence in the transcript of premature termination codons (PTCs) responsible for a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Melfi R,Cancemi P,Chiavetta R,Barra V,Lentini L,Di Leonardo A

    更新日期:2020-07-06 00:00:00

  • Effects of DSPP and MMP20 Silencing on Adhesion, Metastasis, Angiogenesis, and Epithelial-Mesenchymal Transition Proteins in Oral Squamous Cell Carcinoma Cells.

    abstract::Recent reports highlight the potential tumorigenic role of Dentin Sialophosphoprotein (DSPP) and its cognate partner Matrix Metalloproteinase 20 (MMP-20) in Oral Squamous Cell Carcinomas (OSCCs). However, the function/mechanism of these roles is yet to be fully established. The present study aimed to investigate the e...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Aseervatham J,Ogbureke KUE

    更新日期:2020-07-02 00:00:00

  • ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    abstract::The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Bahar E,Kim H,Yoon H

    更新日期:2016-09-15 00:00:00

  • Biophysical Analysis of Lipopolysaccharide Formulations for an Understanding of the Low Endotoxin Recovery (LER) Phenomenon.

    abstract::Lipopolysaccharides (LPS, endotoxin) are complex and indispensable components of the outer membrane of most Gram-negative bacteria. They represent stimuli for many biological effects with pathophysiological character. Recombinant therapeutic proteins that are manufactured using biotechnological processes are prone to ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Correa W,Brandenburg K,Zähringer U,Ravuri K,Khan T,von Wintzingerode F

    更新日期:2017-12-16 00:00:00

  • Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation.

    abstract::Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Lkhagvadorj K,Zeng Z,Meyer KF,Verweij LP,Kooistra W,Reinders-Luinge M,Dijkhuizen HW,de Graaf IAM,Plösch T,Hylkema MN

    更新日期:2020-12-26 00:00:00

  • Histone Posttranslational Modifications of CD4⁺ T Cell in Autoimmune Diseases.

    abstract::The complexity of immune system is tempered by precise regulation to maintain stabilization when exposed to various conditions. A subtle change in gene expression may be magnified when drastic changes are brought about in cellular development and function. Posttranslational modifications (PTMs) timely alter the functi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Wang Z,Yin H,Lau CS,Lu Q

    更新日期:2016-09-22 00:00:00

  • Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity.

    abstract::Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxye...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Grossman CE,Carter SL,Czupryna J,Wang L,Putt ME,Busch TM

    更新日期:2016-01-14 00:00:00

  • The Roles of Sodium-Independent Inorganic Phosphate Transporters in Inorganic Phosphate Homeostasis and in Cancer and Other Diseases.

    abstract::Inorganic phosphate (Pi) is an essential nutrient for the maintenance of cells. In healthy mammals, extracellular Pi is maintained within a narrow concentration range of 0.70 to 1.55 mM. Mammalian cells depend on Na+/Pi cotransporters for Pi absorption, which have been well studied. However, a new type of sodium-indep...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Lacerda-Abreu MA,Russo-Abrahão T,Meyer-Fernandes JR

    更新日期:2020-12-06 00:00:00

  • DNA and RNA quadruplex-binding proteins.

    abstract::Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Se...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Brázda V,Hároníková L,Liao JC,Fojta M

    更新日期:2014-09-29 00:00:00

  • Chromosome Missegregation in Single Human Oocytes Is Related to the Age and Gene Expression Profile.

    abstract::The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of aneuploid pregnancies. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood. To gain new insight into the molecular basis of age-...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Barone S,Sarogni P,Valli R,Pallotta MM,Silvia G,Frattini A,Khan AW,Rapalini E,Parri C,Musio A

    更新日期:2020-03-12 00:00:00

  • Serum Matrix Metalloproteinases and Left Atrial Remodeling-The Hoorn Study.

    abstract::Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Par...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Linssen PBC,Brunner-La Rocca HP,Schalkwijk CG,Beulens JWJ,Elders PJM,van der Heijden AA,Slieker RC,Stehouwer CDA,Henry RMA

    更新日期:2020-07-13 00:00:00

  • Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry.

    abstract::Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the trans...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Hu X,Yang J,Li C

    更新日期:2015-12-02 00:00:00

  • Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression.

    abstract::Obesity is a worldwide epidemic problem and correlates to varieties of acute or chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. An increase of leptin, a kind of adipokine, in lean mice plasma has been found to impair immune responses and...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Hsu PS,Lin CM,Chang JF,Wu CS,Sia KC,Lee IT,Huang KY,Lin WN

    更新日期:2019-03-02 00:00:00

  • Dry Eye Disease and Tear Cytokine Levels-A Meta-Analysis.

    abstract::Background-It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods-The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Roda M,Corazza I,Bacchi Reggiani ML,Pellegrini M,Taroni L,Giannaccare G,Versura P

    更新日期:2020-04-28 00:00:00

  • Impact of serum chemerin levels on liver functional reserves and platelet counts in patients with hepatocellular carcinoma.

    abstract::Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves i...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Imai K,Takai K,Hanai T,Shiraki M,Suzuki Y,Hayashi H,Naiki T,Nishigaki Y,Tomita E,Shimizu M,Moriwaki H

    更新日期:2014-06-25 00:00:00

  • Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment.

    abstract::Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Buda V,Andor M,Petrescu L,Cristescu C,Baibata DE,Voicu M,Munteanu M,Citu I,Muntean C,Cretu O,Tomescu MC

    更新日期:2017-02-07 00:00:00

  • TRAF6 inhibition rescues dexamethasone-induced muscle atrophy.

    abstract::Tumor necrosis factor receptor-associated factor 6 (TRAF6), a unique E3 ubiquitin ligase and adaptor protein, is involved in activation of various signaling cascades. Recent studies identify TRAF6 as one of the novel regulators of skeletal muscle atrophy. The role of TRAF6 in glucocorticoid-induced muscle atrophy, how...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Sun H,Gong Y,Qiu J,Chen Y,Ding F,Zhao Q

    更新日期:2014-06-20 00:00:00

  • Chemically induced breast tumors in rats are detectable in early stages by contrast enhanced magnetic resonance imaging but not by changes in the acute-phase reactants in serum.

    abstract::The present study was undertaken to develop a rat model for monitoring the early development of breast cancer. Twelve female rats were divided into two groups of six rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer or with bacterial lipopolysaccharide to induce inflammation. Serum samp...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Golbabapour S,Pang WW,George J,Pasupati T,Abdul-Rahman PS,Hashim OH

    更新日期:2011-02-07 00:00:00

  • Combined Effects of Confinement and Macromolecular Crowding on Protein Stability.

    abstract::Confinement and crowding have been shown to affect protein fates, including folding, functional stability, and their interactions with self and other proteins. Using both theoretical and experimental studies, researchers have established the independent effects of confinement or crowding, but only a few studies have e...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Ross ML,Kunkel J,Long S,Asuri P

    更新日期:2020-11-12 00:00:00

  • Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability.

    abstract::Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Chen HF,Chuang HC,Tan TH

    更新日期:2019-05-30 00:00:00

  • Physiological and Metabolomic Responses of Kale to Combined Chilling and UV-A Treatment.

    abstract::Short-term abiotic stress treatment before harvest can enhance the quality of horticultural crops cultivated in controlled environments. Here, we investigated the effects of combined chilling and UV-A treatment on the accumulation of phenolic compounds in kale (Brassica oleracea var. acephala). Five-week-old plants we...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Lee JH,Kwon MC,Jung ES,Lee CH,Oh MM

    更新日期:2019-10-08 00:00:00

  • Proteolipid Protein 2 Overexpression Indicates Aggressive Tumor Behavior and Adverse Prognosis in Human Gliomas.

    abstract::Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell line...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Chen YH,Hueng DY,Tsai WC

    更新日期:2018-10-26 00:00:00

  • The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors.

    abstract::Deregulated microRNA (miRNA) expression profiles and their contribution to carcinogenesis have been observed in virtually all types of human cancer. However, their role in the pathogenesis of rare mesenchymal gastrointestinal stromal tumors (GISTs) is not well defined, yet. In this study, we aimed to investigate the r...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Gyvyte U,Lukosevicius R,Inciuraite R,Streleckiene G,Gudoityte G,Bekampyte J,Valentini S,Salteniene V,Ruzgys P,Satkauskas S,Zviniene K,Kupcinskas J,Skieceviciene J

    更新日期:2020-07-21 00:00:00